Original Article

Response to phenylephrine testing in upper eyelids with ptosis

Digital Journal of Ophthalmology, Vol. 21

a b c a
Grace N. Lee, MD, Li-Wei Lin, MD, Sonia Mehta, MD, and Suzanne K. Freitag, MD
Author affiliations: aDepartment of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston,
Massachusetts;
bLexington Eye Associates, Lexington, Massachusetts;
cDepartment of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia

Abstract
Objective—To evaluate the response of ptotic upper eyelids to topical phenylephrine 10%.
Methods—The medical records of patients referred for ptosis evaluation over an 18-month period were
retrospectively reviewed. Seventy-seven ptotic upper eyelids with aponeurotic dehiscence in 47 patients
were given 1 drop of 10% phenylephrine. Margin-to-reflex distance 1 (MRD1) and levator excursion were
recorded and photography of lid height was performed both pre- and 5 minutes post-phenylephrine testing.
Results—A total of 77 ptotic upper eyelids of 47 patients were included. In 22% of lids, phenylephrine
testing produced no response; in 18%, lid elevation of 0.5–1 mm; in 35%, elevation of 1.5–2 mm; and in
25%, elevation of > 2 mm. Subgroup analyses revealed a higher proportion of response in cases of mild to
moderate ptosis compared with cases of severe ptosis. The amount of levator function in these cases of apo-
neurotic dehiscence did not correlate with the amount of response to phenylephrine.
Conclusions—A majority of ptotic eyelids, regardless of levator function, responded to topical phenyl-
ephrine, which has been demonstrated to be necessary for successful Müller’s muscle resection ptosis
repair. While the severity of ptosis was linked to eyelid response to phenylephrine, the degree of levator
function did not appear to affect an eyelid’s response to phenylephrine. In this study cohort, phenylephrine
Digital Journal of Ophthalmology, Vol. 21

was shown to stimulate Müller’s muscle contraction independently of levator function.

Blepharoptosis is among the most commonly encoun-
tered eyelid disorders in ophthalmology. Multiple surgi-
cal options exist for its treatment, including Müller’s
muscle resection (MMR), first introduced by Putterman
and Urist in 1975 as a modification of the Fasanella-
Servat procedure.1,2 It is well documented that preoper-
ative response to topical phenylephrine is an important
criterion for successful MMR ptosis repair.1,3–7 During
phenylephrine testing, exposure to topical phenylephr-
ine, an alpha adrenergic agonist, contracts the sympa-
thetically innervated Müller’s muscle and elevates the
lid. Studies have shown that maximal results from Mül-
ler’s muscle resection are seen in patients with both
good response to phenylephrine testing and good levator
function.8 The sympathomimetic effect of phenylephrine
theoretically involves only the action of Müller’s mus-
cle, so it is curious that levator function also affects the
outcome of Müller’s muscle resection. This may be
attributable to the probability that Müllerectomy also
includes some degree of plication of the posterior aspect
of the levator aponeurosis.8,9 To our knowledge, the
present study is the first to evaluate the response to topi-
cal phenylephrine testing in upper eyelids with aponeur-
otic ptosis with various degrees of levator excursion and
to describe the proportion of responders and quantify the
response.
Subjects and Methods
The medical records of all patients with aponeurotic
dehiscence referred to one author (SKF) for ptosis eval-
uation over an 18-month period, from January 2006 to
June 2007, were retrospectively reviewed. These
patients were subdivided into different ptosis etiologies

Published September 13, 2015.

Copyright ©2015. All rights reserved. Reproduction in whole or in part in any form or medium without expressed written permission of the
Digital Journal of Ophthalmology is prohibited.
doi:10.5693/djo.01.2015.05.001
Correspondence: Suzanne K. Freitag, MD, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243
Charles St. 10th Floor, Boston, MA 02114 (email: Suzanne_Freitag@meei.harvard.edu).
 36

including age-related, postoperative, and contact lens– Table 1. Overall response to phenylephrine (ΔMRD1) in
related ptosis. Some patients had multifactorial contribu- millimeters
tions to their aponeurotic ptosis and thus were incorpo-
rated into more than one subcategory. For example, an
elderly patient with bilateral age-related levator dehis-
cence ptosis had worse ptosis on one side after cataract
Digital Journal of Ophthalmology, Vol. 21

surgery: one lid was categorized as age-related aponeur-

otic ptosis and the contralateral lid was categorized as
both age-related and postoperative aponeurotic ptosis.
Patients with no other attributable cause for ptosis and
MRD1 minus pre-phenylephrine MRD1. The ΔMRD1
no evidence of associated neuropathy or myopathy were
was categorized as follows: zero, 0.5–1 mm, 1.5–2 mm,
determined to have aponeurotic ptosis and were inclu-
and >2 mm. Additional analyses compared response to
ded. Specifically, patients with trauma to the eyelid, cra-
phenylephrine with severity of ptosis, etiology of levator
nial nerve palsies, tumors causing mechanical ptosis,
dehiscence, and levator function. Statistical significance
congenital ptosis, and Horner’s syndrome were exclu-
of the difference in the ΔMRD1 within subgroups (etiol-
ded. This study was conducted under the auspices of the
ogy of ptosis, severity of ptosis, levator function) was
Boston University and Massachusetts Eye and Ear Insti-
analyzed using the Kruskal-Wallis nonparametric analy-
tutional Review Board, in compliance with the rules and
regulations of the US Health Insurance Portability and sis of variance (ANOVA) test.
Accountability Act of 1996 and in adherence to all other
relevant federal and state laws. Results
In the phenylephrine test, 1 drop of phenylephrine 10% A total of 47 patients (23 males [49%]) with 77 ptotic
solution was placed at the superior limbus of each eye upper eyelids were evaluated. All patients had ptosis due
with a ptotic eyelid.1 The drop was placed with the eye to aponeurotic dehiscence. Mean patient age with stand-
in downgaze, with the examiner’s finger elevating the ard deviation was 67.1 ± 17.1 years (range, 15–86 years)
upper eyelid. Margin-to-reflex distance 1 (MRD1) was
Of the 77 ptotic lids, 70 (91%) were due to age-related
recorded by the author and photography was performed
changes, 26 (34%) had a history of intraocular surgery,
both before and 5 minutes after phenylephrine testing.
and 4 (5%) were attributable to contact lens wear. Of the
MRD1 was measured by one author (SKF) by assessing
77 ptotic lids, 20 (26%) were categorized as a combina-
Digital Journal of Ophthalmology, Vol. 21

the distance between the pupillary light reflex from a

muscle light to the margin of the upper eyelid using a
millimeter ruler held adjacent to the patient’s lateral can-
thus. A finger was placed over the patient’s brow to
ensure frontalis relaxation. Two observers reviewed the
photographs to determine MRD1 pre- and post-phenyl-
ephrine placement. Clinical measurements and photo-
graphic determinations were compared and in all cases
were within 1 mm of each other. If there was a discrep-
ancy, the mean of the two measurements was used. Clin-
ical measurements of levator function involved the
examiner stabilizing the patient’s frontalis muscle with a
finger placed above the brow while the patient looked
from far downgaze to far upgaze. The patient’s age, sex,
prior ocular history, cause of ptosis, severity of ptosis,
levator function, and response to phenylephrine were
recorded. Severity of ptosis was categorized as follows:
mild ptosis, MRD1 of 2–3 mm; moderate ptosis, MRD1
of 0.5–1.5 mm; and severe ptosis, MRD1 of ≤0 mm.
Data Analysis
Response to phenylephrine was defined as the change in
MRD1, where ΔMRD1 is equal to post-phenylephrine
tion of age-related and postoperative, and 3 were a com-
bination of age-related and contact lens wear.
Of the 77 eyelids, 13 (17%) had mild ptosis; 39 (51%),
moderate ptosis; and 25 (33%), severe ptosis Seventeen
eyelids (22%) had a ΔMRD1 of 0 mm; 14 (18%), a
ΔMRD1 of 0.5–1 mm; 27 (35%), a ΔMRD1 of 1.5–2
mm; and 19 (25%), a ΔMRD1 of >2 mm (Table 1).
Response to phenylephrine was analyzed for each
severity subgroup (Figure 1). Of 13 eyelids with mild
ptosis, 12 (92%) had some response to phenylephrine.
Of 39 eyelids with moderate ptosis, 31 (80%) had some
response to phenylephrine. However, of 25 eyelids with
severe ptosis, 17 (68%) had some response to phenyl-
ephrine. The difference in response across ptosis
severity subgroups was not statistically significant (P =
0.734). Response to phenylephrine was also analyzed for
ptosis etiology subgroups (Figure 2). Eyelids with age-
related aponeurotic ptosis were compared with lids with
postoperative and contact lens–related ptosis. Of lids
with postoperative ptosis, 77% had at least 1.5 mm of
elevation. On the other hand, among eyelids without sur-
 Lee et al. 37
Digital Journal of Ophthalmology, Vol. 21

Figure 1. Response to phenylephrine (Δ margin reflex distance 1 [MRD1]) by severity of ptosis.

Digital Journal of Ophthalmology, Vol. 21

Figure 2. Response to phenylephrine (ΔMRD1): ptosis etiology subgroup analysis.

gery and only age-related changes, 42% had at least 1.5 Table 2. Levator function (N = 47 patients, 77 eyelids)
mm of elevation. There were only 4 eyelids with contact
lens–involving ptosis. All 4 had at least 1.5 mm of ele-
vation. The difference between these three groups was
statistically significant (P = 0.012) Finally, response to
phenylephrine was analyzed for varying amounts of
levator function. Eyelids were classified under three cat-
egories of levator function: excellent levator function at all to phenylephrine (Figure 3). The difference in
(≥15 mm of excursion), good levator function (11–14 response to phenylephrine across levator function
mm of excursion), and fair levator function (≤10 mm of groups was not statistically significant (P = 0.768).
excursion). Forty-three of eyelids (56%) had excellent
levator function; 36%, good levator function; and 8%, No adverse effects from phenylephrine testing were
poor levator function (Table 2). noted in any patients in this study.

Among eyelids with excellent or good levator function,

Discussion
80% had some response to phenylephrine and 61% had
at least 1.5 mm of response to phenylephrine. Of the 6 That response to topical phenylephrine is necessary for a
eyelids with fair levator function, 50% did not respond successful outcome in Müller’s muscle resection ptosis

Digital Journal of Ophthalmology, Vol. 21
Figure 3. Response to phenylephrine (ΔMRD1): levator function subgroup analysis.
repair has been well documented.1,2 During phenylephr-
ine testing, the sympathetically innervated Müller’s
muscle contracts and elevates the lid when exposed to
topical phenylephrine, an alpha-adrenergic agonist. We
are unaware of previous studies addressing the question
of what proportion of ptotic eyelids with aponeurotic
dehiscence respond to topical phenylephrine and
whether there are any predictive factors, such as severity
of ptosis, amount of levator function, or history of prior
intraocular surgery.
Overall, 78% of eyelids in this study had some response
to phenylephrine, and 60% responded ≥1.5 mm. Thus
more than half of the eyelids tested had enough response
Digital Journal of Ophthalmology, Vol. 21
to be considered candidates for Müller’s muscle resec-
tion surgery.
Lids with mild ptosis had a phenylephrine response rate
of 88%, with 69% responding ≥1.5 mm. These lids with
mild ptosis are often considered to be the best candidates
for Müller’s muscle resection surgery, because this tech-
nique usually will not raise the lid more than 2 mm.1,4,5
Thirty-two percent of eyelids with severe ptosis did not
respond to phenylephrine testing. However, the same
percentage of severely ptotic eyelids (32%) responded
exuberantly (2.5–3.5 mm) to phenylephrine testing.
Investigation of the demographics, etiology of ptosis,
and the degree of levator function within this subgroup
of severe ptosis showed no correlation with the response
to phenylephrine. Thus, there may still be a role for
attempting phenylephrine testing on patients with severe
ptosis and considering conjunctival Müller’s muscle
resection based on these findings.
Ninety-six percent of eyelids in postoperative eyes
responded to phenylephrine testing. Additionally, all
eyelids (4/4) with contact lens–related ptosis had at least
38
1.5 mm response to phenylephrine, including 2 with
severe ptosis. The difference in response seen between
these groups was statistically significant. It has been
postulated that cataract surgery contributes to the onset
of ptosis due to the stretch of the levator from the specu-
lum countering the strength of the orbicularis. However,
manipulation of the upper eyelid when placing postoper-
ative eyedrops may also contribute to the development
of ptosis, as when the upper eyelid is stretched when
placing a contact lens.10
A majority of the eyelids (92%) had ptosis with good or
excellent levator excursion. There was no statistically
significant difference between the degree of levator
function compared to the amount of response to phenyl-
ephrine. Georgescu et al showed that in 4 eyelids with
fair levator function (4–8 mm) and satisfactory response
to phenylephrine, they were able to achieve a good
result (mean MRD1, 3.38) after conjunctival Müller’s
muscle resection.11 Thus indiscriminate of levator func-
tion, the response to phenylephrine may be the most pre-
dictive element for a successful Müller’s muscle resec-
tion.
These trends in phenylephrine response may help sur-
geons anticipate which patients are likely to benefit from
preoperative phenylephrine testing. This can save time
in the clinic and may help avoid the risk, albeit low, of
adverse events, which have been reported with topical
phenylephrine testing, including hypertension exacerba-
tion and cardiac arrest.12 Thus, avoidance of testing on a
subgroup of patients with a cardiac history, such as
supraventricular tachycardia or volatile hypertension,
should be considered.
There has been some discrepancy regarding the techni-
que of phenylephrine drop placement. According to Put-
 Lee et al.
terman’s publications, the drop was placed between the
superior globe and the upper eyelid, aiming toward the
superior fornix1; however, other accounts, including
Ben Simon et al describe a technique of instilling the
drop in the inferior fornix.13 Whatever the location of
the drop placement, we felt that placement anywhere
Digital Journal of Ophthalmology, Vol. 21
along the ocular surface would have the same effect on
the upper eyelid.
We conclude, based on our retrospective study, that pre-
operative phenylephrine testing in upper eyelid ptosis
has a greater response rate and greater amount of lid ele-
vation in patients with mild ptosis and patients with pto-
sis secondary to prior intraocular surgery. Patients with
severe ptosis had a lower response rate to phenylephrine
testing and may be poorer candidates for Müller’s mus-
cle resection ptosis repair; however, we also found that it
is possible to elicit 2.5–3.5 mm of response in patients
with severe ptosis, which may influence a surgeon’s
decision to perform a Müller’s muscle resection. More-
over, patients with lower than normal levator excursion
may still be candidates for Müller’s muscle resection in
light of the response to phenylephrine observed in our
study.
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